This is an application for a renewal of a Program Project Grant, entitled, "MOLECULAR MECHANISMS OF CONTRACTION". The projects are designed to elucidate the molecular processes by which critical systems in the heart regulate the intracellular calcium levels and thus, myocardial contractility. The information derived is fundamental towards the understanding of the factors involved in a dysfunctioning heart and will be valuable in the synthesis of new molecules that may prevent or reverse the disease processes. The six projects include studies on human heart voltage-dependent calcium channels, human Na, K-ATPase, myosin, troponin I, phospholamban in the sarcoplasmic reticulum, and a regulatory atrial apolipoprotein. All the projects are directed towards elucidating structure-function relationships and understanding regulatory mechanisms at the molecular level. All use molecular biological strategies and at least three are designed to extend their studies to an in vivo model and produce transgenic mice with specific characteristics. The scientific cores include molecular biology, protein chemistry and transgenic animal cardiovascular dynamics.